Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2025;15(4):5595 1 Eruptive Clear Cell Acanthomas with Atypical Dermoscopic Features Luca Ambrosio1,2, Antonio Di Guardo1,2, Vincenzo Roberti3, Andrea Ascione4, Claudio Conforti2, Giovanni Pellacani1 1 Department of Medical and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy 2 IDI-IRCCS, Dermatological Research Hospital, Rome, Italy 3 Department of Plastic, Reconstructive and Cosmetic Surgery, “Campus Bio-Medico” University, Rome, Italy 4 Department of Experimental Medicine, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy Key words: Clear Cell Acanthoma, Eruptive, Atypical Dermoscopic Features, Dermoscopy, Clinical Observations Citation: Ambrosio L, Di Guardo A, Roberti V, Ascione A, Conforti C, Pellacani G. Eruptive Clear Cell Acanthomas With Atypical Dermoscopic Features. Dermatol Pract Concept. 2025;15(4):5595. DOI: https://doi.org/10.5826/dpc.1504a5595 Accepted: June 29, 2025; Published: October 2025 Copyright: ©2025 Ambrosio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Antonio Di Guardo, MD, Department of Medical and Cardiovascular Sciences, “Sapienza” University of Rome, 00161 Rome, Italy; IDI-IRCCS, Dermatological Research Hospital, 00167 Rome, Italy. ORCID ID: 0000-0002-0117-346X. E-mail: diguardo.antonio96@gmail.com; antonio.diguardo@uniroma1.it Introduction Clear cell acanthoma (CCA) is a rare, benign epidermal tu- mor first described in 1962 by Degos et al. [1]. It is charac- terized by glycogen-containing epithelial cells and presents as dome-shaped, reddish papules or papule-nodules [2]. A rare eruptive form, with the presence of more than 30 le- sions, has been described [3]. We report a case of eruptive clear cell acanthomas (ECCA) in a patient with a family his- tory of multiple CCAs. Case Presentation A 67-year-old male presented to our dermatology clinic with multiple asymptomatic skin lesions of varying morphology with a gradual appearance over the preceding several years. His family history revealed that his brother had multiple CCAs excised years earlier. Clinical examination identified over 50 well-demarcated, bright red-to-brown papules and nodules, ranging from 2 to 10 mm, located primarily on the lower extremities and trunk. Some lesions exhibited a col- larette of peripheral scaling. Dermoscopy of the suspected CCAs revealed dotted and globular vascular structures ar- ranged in a “pearl necklace pattern,” while others exhib- ited “wafer-like” crusty scales. Some lesions also exhibited non-specific features such as pink areas with irregularly distributed vessels (comma-shaped, linear irregular, or glo- merular) accompanied by white-yellow scales (Figure 1). An incisional biopsy of three suspected lesions was performed. Histopathological examination revealed marked acanthosis composed of glycogen-rich clear cells (Figure 2). The pap- illary dermis displayed tortuous, ectatic vessels surrounded by a moderate lymphohistiocytic infiltrate. These findings, together with the patient’s history and clinical presentation, 2 Research Letter | Dermatol Pract Concept. 2025;15(4):5595 confirmed the diagnosis of ECCAs. Given the patient’s ex- tensive lesions and reluctance to undergo comprehensive treatment, only lesions with suspicious dermoscopic features were excised, and regular follow-up was arranged. Conclusion This case underscores the importance of dermoscopy in dis- tinguishing CCAs from mimickers like basal cell carcinomas or squamous cell carcinomas. The characteristic “pearl neck- lace” vascular pattern and keratotic scales serve as helpful diagnostic clues, particularly in atypical or eruptive cases. Dermoscopy also aids in identifying lesions that warrant biopsy or excision, as in this case, where only lesions with suspicious dermoscopic features were surgically removed. Additionally, this report highlights a rare familial occurrence of ECCAs characterized by the appearance of multiple le- sions in both the patient and his brother. Eruptive CCAs are an uncommon clinical variant, with more than 30 lesions often appearing progressively over time [4]. Additionally, this familial occurrence of ECCA raises questions about ge- netic predisposition or shared environmental triggers. While the exact pathogenesis of CCAs remains unclear, hypotheses include metabolic enzyme defects, localized inflammatory Figure 1. Dermoscopy on polarized mode of eight lesions suspected of being clear cell acanthomas. Some lesions ex- hibit the classic “pearl necklace” appearance, others display scaling and hyperkeratosis, while some show a pinkish coloration with dotted vessels. Figure 2. Histology shows the typical features of a clear cell acanthoma. The lesion is characterized by acanthosis, cells with clear cytoplasm, and by abrupt transition with the nearby normal epidermis. (A: H&E, original magnifi- cation 1.25x; B: H&E, original magnification 20x). Research Letter | Dermatol Pract Concept. 2025;15(4):5595 3 responses, and epidermal glycogen accumulation [3-5]. Future research exploring genetic pathways and inflamma- tory markers may further clarify the mechanisms underlying familial and eruptive variants of CCA. Ethical Approval: The study was a retrospective evaluation conducted in accordance with the principles of the Declara- tion of Helsinki and the International Council for Harmoniza- tion and Good Clinical Practice guidelines. Written informed consent was obtained from the patient to publish this paper. References 1. Degos R, Delort J, Civatte J, Poiares Baptista A. Epidermal tumor with an unusual appearance: clear cell acanthoma. Ann Derma- tol Syphiligr. 1962;89:361–371. French. PMID: 14026439. 2. Monari P, Farisoglio C, Gualdi G, Botali G, Ungari M, Calzavara-Pinton P. Multiple eruptive clear cell acanthoma. J Dermatol Case Rep. 2010 Nov 19;4(2):25-7. DOI: 10.3315 /jdcr.2010.1048. PMID: 21886743. 3. García-Gavín J, González-Vilas D, Montero I, Rodríguez-Pazos L, Pereiro MM, Toribio J. Disseminated eruptive clear cell ac- anthoma with spontaneous regression: further evidence of an inflammatory origin? Am J Dermatopathol. 2011 Aug;33(6):599-602. DOI: 10.1097/DAD.0b013e3181f078e0. PMID: 21317609. 4. Innocenzi D, Barduagni F, Cerio R, Wolter M. Disseminated eruptive clear cell acanthoma—a case report with review of the literature. Clin Exp Dermatol. 1994 May;19(3):249-53. DOI: 10.1111/j.1365-2230.1994.tb01179.x. PMID: 8033390. 5. Zaballos P, Lara-Valencia P, Van Den Bossche K, et al. Clear Cell Proliferations of the Skin: A Histopathologic Review. Am J Dermatopathol. 2021 Sep 1;43(9):607-636. DOI: 10.1097/DAD .0000000000001881. PMID: 34411018.